A compound having a generic name of metoclopramide is widely known as a compound having nature of promoting the movement of stomach, but induces extrapyramidal disorder and other undesirable disorders due to action on central nervous system. In addition, a compound having a generic name of cisapride has been put into practice as a digestive tract movement activator, but use thereof has been stopped due to inducement of ventricular arrhythmia.
4-Amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrrolidinyl]benzamide (also referred to as TKS159 in some cases) or an acid addition salt thereof which is said to have no or extremely weak action on central nervous system is known as a compound having action of promoting the movement of the digestive tract, inter alia, stomach (JP-A-17434/1993). However, the present applicant progressed development of TKS159 which is a representative compound of the invention of the above patent and, when TKS159 was orally administered repeatedly in a safety test using an experimental animal, inter alia, a beagle dog, findings of disorders such as thrombus formation, arteritis, encephalomalacia and the like were observed. After all, occurrence of such disorders truly shows that TKS159 is not suitable for use as a medicine. The present inventors thought that various disorders which had not appeared in a mouse or a rat are findings of disorders caused by 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-2-hydroxymethyl-4-pyrrolidinyl]benzamide or an acid addition salt thereof found to be a metabolite of the compound specifically produced in a beagle dog and they have repeatedly administered 4-amino-5-chloro-2-methoxy-N-[(2S, 4S)-2-hydroxymethyl-4-pyrrolidinyl]benzamide or an acid addition salt thereof to a beagle dog. Unexpectedly, it was found out that findings of various disorders seen upon administration of TKS159 were not observed. Moreover, it was found out that 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-2-hydroxymethyl-4-pyrrolidinyl]benzamide or an acid addition salt thereof is a compound having the ability of improving the movement of the digestive tract equivalent to or superior over that of TKS159 or an acid addition salt thereof. That is, it was found out that 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-2-hydroxymethyl-4-pyrrolidinyl]benzamide or an acid addition salt thereof which can avoid occurrence of disorders such as thrombus formation, arteritis, encephalomalacia and the like can be effectively used as an ameliorant for improving the movement of the digestive tract containing this compound as an active ingredient. Needless to say, it is natural that desired attribute of a drug used in treatment is sufficient possession of required action, and it is widely sought to provide a drug from which occurrence of not preferable action which is reportedly impossible to avoid due to inevitable attendance to the drug, has been removed. In diseases other than diseases directly influencing on a life, such the tendency is further intense. It is widely known that there are many cases where although a drug has sufficient required action, since occurrence of a few unavoidable not preferable actions can not be avoided, it could not actually play a role as a therapeutic drug. In addition, although the aforementioned patent describes 4-amino-5-chloro-2-methoxy-N-(5-hydroxymethylpyrrolidin-3-yl)benzamide, but 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-2-hydroxymethyl-4-pyrrolidinyl]benzamide is a novel compound as stereo isomer or optical isomer.